Intra-erythrocytic vacuoles in asplenic patients: elusive genesis and original clearance of unique organelles

The spleen plays a dual role of immune response and the filtration of red blood cells (RBC), the latter function being performed within the unique microcirculatory architecture of the red pulp. The red pulp filters and eliminates senescent and pathological RBC and can expell intra-erythrocytic rigid bodies through the so-called pitting mechanism. The loss of splenic function increases the risk of infections, thromboembolism, and hematological malignancies. However, current diagnostic tests such as quantification of Howell-Jolly Bodies and splenic scintigraphy lack sensitivity or are logistically demanding. Although not widely available in medical practice, the quantification of RBC containing vacuoles, i.e., pocked RBC, is a highly sensitive and specific marker for hyposplenism. The peripheral blood of hypo/asplenic individuals contains up to 80% RBC with vacuoles, whereas these pocked RBC account for less than 4% of RBC in healthy subjects. Despite their value as a spleen function test, intraerythrocytic vacuoles have received relatively limited attention so far, and little is known about their origin, content, and clearance. We provide an overview of the current knowledge regarding possible origins and mechanisms of elimination, as well as the potential function of these unique and original organelles observed in otherwise “empty” mature RBC. We highlight the need for further research on pocked RBC, particularly regarding their potential function and specific markers for easy counting and sorting, which are prerequisites for functional studies and wider application in medical practice

Impact of Temporary Nitrogen Deprivation on Tomato Leaf Phenolics

Reducing the use of pesticides represents a major challenge of modern agriculture. Plants synthesize secondary metabolites such as polyphenols that participate in the resistance to parasites. The aim of this study was to test: (1) the impact of nitrogen deficiency on tomato (Solanum lycopersicum) leaf composition and more particularly on two phenolic molecules (chlorogenic acid and rutin) as well as on the general plant biomass; and (2) whether this effect continued after a return to normal nitrogen nutrition. Our results showed that plants deprived of nitrogen for 10 or 19 days contained higher levels of chlorogenic acid and rutin than control plants. In addition, this difference persisted when the plants were once again cultivated on a nitrogen-rich medium. These findings offer interesting perspectives on the use of a short period of deprivation to modulate the levels of compounds of interest in a plant

Influence of root and leaf traits on the uptake of nutrients in cover crops

Aims: Cover crops play an important role in soil fertility as they can accumulate large amounts of nutrients. This study aimed at understanding the nutrient uptake capacity of a wide range of cover crops and at assessing the relevance of acquisition strategies. Methods: A field experiment was conducted to characterize 20 species in terms of leaf and root traits. Plant traits were related to nutrient concentration and shoot biomass production with a redundancy analysis. Acquisition strategies were identified using a cluster analysis. Results: Root systems varied greatly among cover crop species. Five nutrient acquisition strategies were delineated. Significant amounts of nutrients (about 120 kg ha−1 of nitrogen, 30 kg ha−1 of phosphorus and 190 kg ha−1 of potassium) were accumulated by the species in a short period. Nutrient acquisition strategies related to high accumulations of nutrients consisted in either high shoot biomass and root mass and dense tissues, or high nutrient concentrations and root length densities. Species with high root length densities showed lower C/N ratios. Conclusions: The same amounts of nutrients were accumulated by groups with different acquisition strategies. However, their nutrient concentrations offer different perspectives in terms of nutrient release for the subsequent crop and nutrient cycling improvement

Imidazole propionate is increased in diabetes and associated with dietary patterns and altered microbial ecology

Microbiota-host-diet interactions contribute to the development of metabolic diseases. Imidazole propionate is a novel microbially produced metabolite from histidine, which impairs glucose metabolism. Here, we show that subjects with prediabetes and diabetes in the MetaCardis cohort from three European countries have elevated serum imidazole propionate levels. Furthermore, imidazole propionate levels were increased in subjects with low bacterial gene richness and Bacteroides 2 enterotype, which have previously been associated with obesity. The Bacteroides 2 enterotype was also associated with increased abundance of the genes involved in imidazole propionate biosynthesis from dietary histidine. Since patients and controls did not differ in their histidine dietary intake, the elevated levels of imidazole propionate in type 2 diabetes likely reflects altered microbial metabolism of histidine, rather than histidine intake per se. Thus the microbiota may contribute to type 2 diabetes by generating imidazole propionate that can modulate host inflammation and metabolism

Predictors of hospital discharge and mortality in patients with diabetes and COVID-19: updated results from the nationwide CORONADO study

AIMS/HYPOTHESIS: This is an update of the results from the previous report of the CORONADO (Coronavirus SARS-CoV-2 and Diabetes Outcomes) study, which aims to describe the outcomes and prognostic factors in patients with diabetes hospitalised for coronavirus disease-2019 (COVID-19). METHODS: The CORONADO initiative is a French nationwide multicentre study of patients with diabetes hospitalised for COVID-19 with a 28-day follow-up. The patients were screened after hospital admission from 10 March to 10 April 2020. We mainly focused on hospital discharge and death within 28 days. RESULTS: We included 2796 participants: 63.7% men, mean age 69.7 ± 13.2 years, median BMI (25th-75th percentile) 28.4 (25.0-32.4) kg/m(2). Microvascular and macrovascular diabetic complications were found in 44.2% and 38.6% of participants, respectively. Within 28 days, 1404 (50.2%; 95% CI 48.3%, 52.1%) were discharged from hospital with a median duration of hospital stay of 9 (5-14) days, while 577 participants died (20.6%; 95% CI 19.2%, 22.2%). In multivariable models, younger age, routine metformin therapy and longer symptom duration on admission were positively associated with discharge. History of microvascular complications, anticoagulant routine therapy, dyspnoea on admission, and higher aspartate aminotransferase, white cell count and C-reactive protein levels were associated with a reduced chance of discharge. Factors associated with death within 28 days mirrored those associated with discharge, and also included routine treatment by insulin and statin as deleterious factors. CONCLUSIONS/INTERPRETATION: In patients with diabetes hospitalised for COVID-19, we established prognostic factors for hospital discharge and death that could help clinicians in this pandemic period. TRIAL REGISTRATION: Clinicaltrials.gov identifier: NCT04324736

Mortality from gastrointestinal congenital anomalies at 264 hospitals in 74 low-income, middle-income, and high-income countries: a multicentre, international, prospective cohort study

Summary Background Congenital anomalies are the fifth leading cause of mortality in children younger than 5 years globally. Many gastrointestinal congenital anomalies are fatal without timely access to neonatal surgical care, but few studies have been done on these conditions in low-income and middle-income countries (LMICs). We compared outcomes of the seven most common gastrointestinal congenital anomalies in low-income, middle-income, and high-income countries globally, and identified factors associated with mortality. Methods We did a multicentre, international prospective cohort study of patients younger than 16 years, presenting to hospital for the first time with oesophageal atresia, congenital diaphragmatic hernia, intestinal atresia, gastroschisis, exomphalos, anorectal malformation, and Hirschsprung’s disease. Recruitment was of consecutive patients for a minimum of 1 month between October, 2018, and April, 2019. We collected data on patient demographics, clinical status, interventions, and outcomes using the REDCap platform. Patients were followed up for 30 days after primary intervention, or 30 days after admission if they did not receive an intervention. The primary outcome was all-cause, in-hospital mortality for all conditions combined and each condition individually, stratified by country income status. We did a complete case analysis. Findings We included 3849 patients with 3975 study conditions (560 with oesophageal atresia, 448 with congenital diaphragmatic hernia, 681 with intestinal atresia, 453 with gastroschisis, 325 with exomphalos, 991 with anorectal malformation, and 517 with Hirschsprung’s disease) from 264 hospitals (89 in high-income countries, 166 in middleincome countries, and nine in low-income countries) in 74 countries. Of the 3849 patients, 2231 (58·0%) were male. Median gestational age at birth was 38 weeks (IQR 36–39) and median bodyweight at presentation was 2·8 kg (2·3–3·3). Mortality among all patients was 37 (39·8%) of 93 in low-income countries, 583 (20·4%) of 2860 in middle-income countries, and 50 (5·6%) of 896 in high-income countries (p<0·0001 between all country income groups). Gastroschisis had the greatest difference in mortality between country income strata (nine [90·0%] of ten in lowincome countries, 97 [31·9%] of 304 in middle-income countries, and two [1·4%] of 139 in high-income countries; p≤0·0001 between all country income groups). Factors significantly associated with higher mortality for all patients combined included country income status (low-income vs high-income countries, risk ratio 2·78 [95% CI 1·88–4·11], p<0·0001; middle-income vs high-income countries, 2·11 [1·59–2·79], p<0·0001), sepsis at presentation (1·20 [1·04–1·40], p=0·016), higher American Society of Anesthesiologists (ASA) score at primary intervention (ASA 4–5 vs ASA 1–2, 1·82 [1·40–2·35], p<0·0001; ASA 3 vs ASA 1–2, 1·58, [1·30–1·92], p<0·0001]), surgical safety checklist not used (1·39 [1·02–1·90], p=0·035), and ventilation or parenteral nutrition unavailable when needed (ventilation 1·96, [1·41–2·71], p=0·0001; parenteral nutrition 1·35, [1·05–1·74], p=0·018). Administration of parenteral nutrition (0·61, [0·47–0·79], p=0·0002) and use of a peripherally inserted central catheter (0·65 [0·50–0·86], p=0·0024) or percutaneous central line (0·69 [0·48–1·00], p=0·049) were associated with lower mortality. Interpretation Unacceptable differences in mortality exist for gastrointestinal congenital anomalies between lowincome, middle-income, and high-income countries. Improving access to quality neonatal surgical care in LMICs will be vital to achieve Sustainable Development Goal 3.2 of ending preventable deaths in neonates and children younger than 5 years by 2030

État des lieux des permanences des soins ambulatoires au Nord-Ouest de l'Étang-de-Berre : Istres, Miramas et Salon-de-Provence

Introduction : l'accès aux soins primaires, hors horaires d’ouverture des cabinets libéraux, apparaît comme un véritable problème avec pour conséquence un nombre croissant de consultations aux urgences pour des soins non « urgents ». En 2012, l’ARS a édité un cahier des charges pour restructurer les Permanences Des Soins Ambulatoires (PDSA) déjà mises en place. Mais certaines d’entre elles ne semblent pas remplir pleinement leur rôle, ce que j’ai pu constater lors de mon stage de SASPAS à Miramas. Qu’en est-il pour les PDSA voisines ?Objectif : c’est l’objet de cette thèse qui fait l'état des lieux des PDSA du Nord-Ouest de l'Étang-de-Berre, avec les villes d’Istres, Miramas et Salon-de-Provence.Méthode : il s’agit d’une étude descriptive, rétrospective, multicentrique, quantitative, dans sa majorité, depuis 2014.Un questionnaire est adressé aux responsables des PDSA pour collecter les informations afin d’établir leur cohérence avec le cahier des charges et mettre en évidence leurs disparités.Résultats : elles diffèrent d’une part, par leur mode de fonctionnement puisque seules deux d’entre elles sont des MMG avec un service d’urgence à proximité. Elles sont fixes, mobiles ou mixtes avec divers modes d’accès. D’autre part, par leur activité : celle de Miramas décline et reste très faible au regard de ses voisines. Enfin, par le nombre d’effecteurs majoritairement en diminution sur la période.Conclusion : Cette organisation reste donc fragile et difficile à appréhender. Elle dépend de leur fonctionnement, du nombre d’effecteurs, de leur visibilité et de leur financement. Pour une meilleure efficacité, une nouvelle réorganisation de ces trois PDSA est à repenser

Structure, fonction et évolution de LEAFY, facteur de transcription clé du développement floral

LEAFY (LFY) est un facteur de transcription central pour le développement des plantes, en particulier pour la floraison chez les angiospermes. LFY est très conservée, même chez les espèces ne portant pas de fleurs. On dispose de nombreuses données génétiques sur LFY et son réseau de régulation chez la plante modèle Arabidopsis thaliana, mais les mécanismes moléculaires impliqués dans son fonctionnement ne sont pas entièrement élucidés. LFY possède deux domaines conservés : un domaine de liaison à l'ADN et un domaine de fonction inconnue en position N-terminal. L'objectif a été de comprendre le rôle du domaine N-terminal et d'étudier l'évolution de la spécificité de liaison à l'ADN de LFY. Nous avons obtenu la structure cristallographique du domaine N-terminal de LFY et découvert qu'il s'agissait d'un domaine SAM (Sterile Alpha Motif) permettant l'oligomérisation de la protéine. Nous avons validé l'importance de cette propriété pour la fonction florale de LFY chez A. thaliana. Nous avons ensuite montré, par des analyses in vitro et in vivo en ChIP-seq que l'oligomérisation influençait la liaison à l'ADN en permettant une liaison coopérative sur plusieurs sites de liaison, en assurant la sélectivité de la protéine vis-à-vis de l'ADN et en permettant l'accès de la protéine à des régions génomiques où la conformation de la chromatine est normalement défavorable à la liaison. Cette étude intégrative a permis de mieux comprendre le fonctionnement de LFY. Des modifications dans les réseaux de régulation de l'expression des gènes sont source de nouveauté et d'évolution. LFY étant très conservée et ne faisant pas partie d'une famille multigénique, nous nous sommes demandé si sa spécificité de liaison à l'ADN avait évoluée. Nous avons montré que LFY était apparue chez les algues multicellulaires et que sa spécificité avait connue au moins deux changements majeurs au cours de l'évolution. Nous avons expliqué ces modifications au niveau moléculaire par des approches de biologie structurale et de biochimie. Nous avons identifié une espèce chez qui LFY a une spécificité relâchée et nous proposons qu'une telle forme ait pu permettre les transitions d'une spécificité à une autre.LEAFY (LFY) is a key transcription factor for plant development, particularly for flowering in angiosperms. LFY is highly conserved in plants, including non-flowering species. Despite a wealth of genetic data about LFY and its regulatory network in the model plant Arabidopsis thaliana, how the protein works at the molecular level is not fully understood. It has two conserved domains: a DNA binding domain and a N-terminal domain of unknown function. My two main projects were to understand the role of the N-terminal domain and to study LFY DNA binding specificity evolution. We obtained LFY N-terminal domain crystal structure and discovered it was a Sterile-Alpha-Motif (SAM) mediating LFY oligomerisation. We validated the importance of that property for flower development in A. thaliana. Using both in vitro analyses and a ChIP-seq experiment, we pointed out that oligomerisation is required for proper DNA binding. It enables cooperative binding on several LFY binding sites, increases the protein selectivity towards DNA and allows LFY to access genomic regions where the chromatin conformation normally prevents binding. This integrative study provides a better understanding of how LFY works. The rewiring of transcriptional networks provides a rich source of evolutionary novelty. As LFY is highly conserved and single copy in most plant genomes, we asked whether its DNA binding specificity had evolved. We showed that LFY was present since multicellular algae and that it underwent at least two major shifts in DNA-binding specificity during plant evolution. We provided a structural explanation for the two newly identified DNA binding modes and we identified a LFY form with a relaxed specificity that could have served as an intermediate between evolutionary transitions.SAVOIE-SCD - Bib.électronique (730659901) / SudocGRENOBLE1/INP-Bib.électronique (384210012) / SudocGRENOBLE2/3-Bib.électronique (384219901) / SudocSudocFranceF